Project Summary/Abstract Nutrition- and obesity-related research is of critical importance given the tremendous impact of metabolic conditions on human health. While nutrition and obesity related research enables investigators to generate many disease-related hypotheses, the technology needed to create disease-relevant models and to test these hypotheses lies outside the expertise of many individual research groups. The Metabolic Phenotyping Core will serve as a single, central access point for NORC-H investigators to enable both model creation in metabolically relevant cell types and detailed phenotypic characterization of human and model-derived samples. The fundamental activities of the core are divided into two central activities, both supported by expert faculty with extensive experience in all Core activities: 1) model generation, which brings genomic targeting and modern genome editing to the hands of all NORC-H investigators, and 2) metabolic phenotyping, ranging from metabolomics to whole-animal physiology. Model generation will make use of state-of-the-art gene targeting resources available at MGH, the Broad Institute, and Harvard University, permitting NORC-H members to model disease-related processes in primary cells, immortalized cells, and patient-derived inducible pluripotent stem cells. Thereafter, the Core's battery of customizable, metabolic phenotyping assays can be employed to characterize human tissue and blood samples, or model-derived samples provided by the investigator or generated by the Core's model-generation activities. The Core has expert capabilities for metabolomics (tandem-mass spectrometric analysis of endogenous metabolites), characterization of metabolism and respiratory activity of cells in culture, analysis of insulin signaling and gene expression, and physiologic characterization of mouse models of human disease. Under the Core, complex analyses and techniques that require expertise and infrastructure that are difficult or impossible for individual laboratories to attain are made readily available to NORC-H investigators. The innovation of the Core, in addition to its ability to provide state- of-the-art analyses to the broad NORC-H membership, is its centralization of resources in the Harvard community to a single access point. This centralization allows NORC-H investigators to ask an innumerable number of nutrition and obesity related research questions with great efficiency and economy. The significance of the Core's activities lie in its ability to encourage both detailed characterization of human samples and to enable translational, mechanistic studies that cannot be conducted in humans. Finally, the Core will serve as a resource to NORC-H membership to consult and provide education on model development and metabolic characterization projects.